The use of lasers in selective photothermolysis has been reported by Greenwald et al., "Comparative Histological Studies of the Tunable Dye (at 577 nm) Laser and Argon Laser: The Specific Vascular Effects of the Dye Laser", The Journal of Investigative Dermatology 77: 305-310, 1981, and by Anderson and Parrish, "Selective Photothermolysis: Precise Microsurgery by Selective Absorption of Pulse Radiation", Science 220: 524-527, 1983. In this technique, targeted tissues are heated by laser light, the wave length of which is selected to be specifically absorbed by the targeted tissues. The laser pulse duration is tailored to the size of the target. Tissues surrounding the targeted structures are spared.
The above studies highlight the need for selecting lasers which meet both the spectral requirements of a given application and pulse duration requirements. It is important that the laser be tunable to select the color of the source to match some spectral property of the targeted tissue. The special spectral features of targets require specific wavelengths, but only require moderate linewidths (1-4 nm) to induce selective effects. Proper laser pulse duration is important to heat target tissue to denature the tissues without boiling or vaporization. The temperature limits are tight, from body temperature of 35 C. to a temperature well below boiling point, about 70 C. Ordinary calorimetry states that temperature rise is proportional to energy and inversely proportional to target volume irrespective of the time it takes to deliver the energy. If thermal diffusivity is added there is a pulse duration criterion and the energy must be deposited quickly to minimize heat dissipation to surrounding tissue. However, selective photothermolysis heat must not be deposited too quickly so as to exceed the boiling point in the targeted zone.
The situation gets more complex if small absorbing chromophores such as hemoglobin in blood cells are used as absorbers to treat blood vessels which are an order of magnitude larger. The radiation must be added at low intensities so as not to vaporize the small cells, left on long enough to heat the blood vessels by thermal diffusion to the point of denaturation and then turned off before the surrounding tissue is damaged.
Some control in intensity is available by the adjustment of the spot size of the pulsed radiation source. A source capable of delivering more than joule is necessary so that spot sizes do not become too tiny with a concomittant increase in treatment time.
The above studies have shown the dye laser to be particularly suited to selective photothermolysis. Dye lasers are readily tunable to selected wave lengths by means of the choice of dye, wavelength selective filters in the cavity and the like. Further, dye lasers can provide high output energies and short pulse durations. Unfortunately, the typical dye laser pulse duration of only a few microseconds or less is too short for many applications using selective photothermolysis. Dye lasers with nanosecond or shorter pulses are preferred for subcellular organelle targeting and microsecond or shorter pulses are preferred for cell targeting. However, dye lasers do not typically provide the millisecond pulses which are best for blood vessels and other small structures.
It is generally recognized that the quenching of a dye laser after microseconds may be due to the accumulation of dye molecules in the triplet state by means of intersystem crossing from the singlet state. Laser action in a dye laser starts from the singlet states. Molecules which cross over to the triplet state often absorb at the laser wavelength and inhibit laser action. The triplet state effect has been investigated and triplet state quenchers have been reported for specific dyes. However, triplet quenchers for all dyes used in lasers have not been identified. But, even with the use of triplet quenchers, pulse durations of several hundred microseconds have only been obtained at low energy outputs of not more than a few tenths of a joule.
A second problem that makes it difficult to generate long pulses in a dye laser is the distortion of the liquid amplifying medium by absorbed, conducted and convected heat from the laser excitation source. Such distortions are unavoidable but must be minimized for laser action to continue for milliseconds.